Inherently, a work titled Pornocrates exudes scandal, intrigue, and allure. Created in 1878 by Felicien Rops, the gouache and pencil piece was displayed at the Les XX exhibition of 1886. Felicien Rops was a wealthy Belgian-born artist who collaborated alongside the likes of Claude Monet, Odilon Redon, and Pierre-Auguste Renoir. Rops’s works articulated more diabolical motifs and grotesque sexual imagery than both his Impressionist and Symbolist contemporaries. As a result, his artworks are far less circulated and research surrounding Rops is scarce. This does not mean he was the only artist creating taboo media, however. Decadent art which depicted debauchery, excess, and sin was fairly present, especially in France. Rops collaborated with many playwrights, authors, and poets at the end of the 19th century, and was surprisingly popular among wealthy socialites of Paris and Brussels. Rops participated in many coalitions of artists across Europe, but the Les XX society is arguably one of the most significant. Artists, authors, and musicians exhibited their works and celebrated individualized aesthetics rather than a unified, nationalistic style. The group rejected a specific political or regional identity, which contributed to the notion of Belgium as a center for the Avant Garde. Rops’s display of Pornocrates elicited shock and commotion among the artists for its uncensored, sexual critique of high society men and women. This project aims to synthesize some of the scholarship surrounding the display of Pornocrates and serves to further highlight the significance of Decadent art in the Fin de Siècle period.

Between 1527 and 1587, three major pattern books were published in Venice: Giovanni Antonio Tagliente’s (c. 1465-1527) embroidery pattern book, Matthio Pagano’s (1515-1588) cutwork lace pattern book, and Federico de Vinciolo’s (active in Paris c. 1587-99) needlework lace pattern book. These three books represent the first of their respective types, and the beginning of a growing social attention toward lacemaking and its use as textile ornament. Each book provides patterns for different types of needlework: embroidery as applied decoration to fabric, cutwork (punto tagliato) as an evolution of embroidery, which involved cutting away the foundation fabric and filling it in with design, and finally, needlework lace (punto in aria), as freely formed design without a fabric foundation. The Venetian attention to dress and outward physical expression necessitated the use of increasing amounts of ornament—prompting the evolution of needlework into punto in aria designs which the city became famous for. Relevant through its additive aesthetic, public demand and commercial opportunities, lace became an essential export for the city of Venice and many women participated in its production, whether within their private homes, in workshops, or in convents. This essay will explore Venetian negotiations with myth and materiality through lacework as an ascendant medium, examining sixteenth-century pattern books and conduct literature as sources of tension and syncretism between written codification and social practice.

Dopamine (DA) neurons found in the ventral tegmental area (VTA) are associated with reward feedback, and dysfunction in DA circuitry is associated with disorders such as Parkinson’s, schizophrenia, bipolar, and addiction to drugs. To adequately treat these diseases, we must have a more complete understanding of how dopamine contributes to emotional processes. This research project addresses this issue by investigating neuropeptide regulation of dopamine neurons in the VTA. The bed nucleus of the stria terminalis (BNST) is a brain region that expresses many neuropeptide genes and sends strong projections to the VTA. We utilized Cre driver lines to isolate neurons that produce the peptides Neurotensin, Neurokinin B, and Corticotropin Releasing Factor. We injected a virus into the BNST that induces the expression of a light activated ion channel and allows us to stimulate axon terminals in the VTA. I then conducted behavioral experiments to assess the effects of activating these peptidergic inputs. Dopamine-dependent behaviors relating to pleasure, reward, and anxiety were measured through the behavioral tests of Real Time Place Preference, operant conditioning, and Open Field respectively. Most likely due to low expression, my behavioral analyses did not yield statistically significant results. Moving forward, it may be necessary to increase viral titer for wider expression. In the future, I intend to use CRISPR/Cas9 technology to isolate neuropeptide function from fast neurotransmitter release in these circuits. This research, by producing findings that help explain how neuropeptides modulate DA neurons, has the potential to generate advances for the understanding and treatment of dopamine-related psychiatric disorders.

Induced pluripotent stem cells (iPSC) have a high potential, for they can be differentiated into any cell type for regenerative medicine, drug discovery, developmental biology, and disease modeling. However, iPSC’s and their differentiated progeny display an undesired variability in their shape, contractile properties, growth rates, etc. Identifying subsets of phenotypes in iPSCs and their differentiated progeny will allow us to optimize tissue models for research. Here, we generated a rainbow reporter line in iPSCs that can track individual cells as they clonally expand and differentiate while providing phenotypic information. Knocking in four copies of a cassette containing three distinct fluorescent proteins allowed the expression of up to eighteen different colors. However, not all colors were present in equal proportion, increasing the probability that distinct lineages could have the same color. To achieve an equal color distribution, colored cells were isolated by sparsely plating a culture of mixed colored cells. After a week of expansion, individual colonies were picked and imaged under a spinning disk microscope to determine the color of the colony and whether it was single lineage or mixed. Viable cell lines were isolated and frozen in stock. These cells will be examined for markers of cell proliferation, pluripotency, apoptosis and quantitative RNA expression analysis to confirm that the color barcoded iPSCs act the same as non-engineered iPSCs. To date, we were able to create eight color barcoded iPSC lines for further experimentation, increasing the concentration limit of colored cells in non-colored cells by five-fold. The next step will engineer 3D tissues by growing iPSC-derived cardiac cells in a mold to simulate in vivo tissue development. Colored coded cells will allow us to track how the initial location/physical stresses/phenotype of an iPSC-derived cardiac cell in an engineered tissue determines its tissue layer and cell type.

The relationship between humans and robots is full of feedback loops: how our brain processes what we see, feel, and act affects how the intelligent machine reacts and vice versa. Understanding this feedback loop will enable us to design better day-to-day automated systems. For instance, operations performed with surgical robots are guided with the surgeon’s movement. My research in the UW BioRobotics Laboratory investigates how the human brain adapts to technology. I programmed a haptic paddle to apply timed forces on human subjects to investigate how uncertainty, in the form of a disturbance, affects response over time. Understanding how human behavior changes is crucial for improving automated systems that can be simulated by the haptic paddle such as cable-driven surgical robots. We apply the haptic paddle to model forces a surgeon may experience during surgery, such as tough tissues or other disturbances, while operating a robotic surgical device. As we measure the participant’s learning curve over longer periods and more trials, the participant builds a better understanding of how to react relative to their force exerted on to the paddle. By increasing our understanding of how the human brain works, we can begin to improve precision of surgical operation.

After neurologic injuries like stroke, users must relearn how to interact with devices to achieve different tasks. However, hand dominance before and after neurologic injury could affect motor learning and recovery. Understanding a) whether hand dominance plays an effect on motor learning and adaptation of predictive (i.e. feedforward) and reactive (i.e. feedback) controllers and b) how motor learning is impacted by which side was affected by stroke is crucial for personalizing rehabilitation techniques. We are currently investigating the effect of hand dominance on motor learning during continuous tasks for users without motor impairments. 10 participants were asked to play a simple trajectory-tracking game, first with their non-dominant hand and then with their dominant hand. We found that participants’ feedback controllers improved with practice for their non-dominant hand (p=0.005), but their feedforward controllers were unchanged (p=0.88). Furthermore, the participants transferred their feedback controller from their non-dominant hand to their dominant hand (p=0.33). This suggests that the non-dominant hand may be more specialized for error correction and impedance control, and that rehabilitation for users who had a right-hemisphere stroke should focus on improving reactive control.

The mobility of autonomous walking robots is an essential characteristic in their operation. Due to currently imposed constraints in battery technology, the optimization of robotic locomotion for energy efficiency is paramount. Previously, elastic payload suspension has been employed to reduce the cost of transportation in a hexapedal robot. Prior results suggest that the optimal load suspension characteristics are a function of robot morphology and locomotion strategy. A payload suspension system that can be easily adjusted would allow for the accommodation of a variety of these morphologies and locomotion strategies. We have designed a tunable suspension system that will allow for experimentally determining optimal suspension characteristics in a cost-effective manner. The design enables continuous adjustment of the suspension stiffness and damping, so optimal parameters can be determined through hardware experimentation. This hardware experimentation allows for the creation of a numerical model for an oscillating payload’s behavior, which can be compared to simulations. We have completed calculations and design of this hardware, and anticipate seeing that the data collected from its usage will verify the utilization of a haptic testing system in robotics development and allow us to determine methods for calculating the best parameters for elastic payload suspension. This verification of simulated data will allow for further research in developing more efficient methods of payload attachment to legged robots, examination of locomotion when carrying payloads, and design of payload management methods.

Recent increases in atmospheric carbon dioxide levels have led to a decrease in the pH of the world’s oceans. These changes in seawater chemistry could have severe consequences for calcifying organisms such as corals. Ocean acidification (OA) poses an imminent threat to the world’s coral reef ecosystems, which could lead to massive reductions in global marine biodiversity. Much of the response of corals to OA is still poorly understood from a detailed physiological perspective, particularly the impact of OA on a fundamental process of skeletal growth called nucleation. Nucleation is the process by which calcium and carbonate ions combine in solution to form a new piece of solid calcium carbonate, which corals use to build their skeleton. While calcification has been measured in corals, the specific step of nucleation has not been quantified and has the potential to be more sensitive to ocean acidification. Coral fragments of Stylophera pistillata and Acropora microphthalma were grown on microscope slides secured in petri dishes in normal ocean conditions suitable for growth. Half of the fragments will be placed into another tank that has constant alkalinity and a set pH of about 7.8 controlled with bubbling air at 800ppm carbon dioxide into the water, the predicted level of atmospheric carbon dioxide in 2100 with the current rate of emissions. This will allow for a big enough change in pH to clearly determine if nucleation is affected by lower pH. With an inverted microscope, the calcifying space was visible through the glass slides, and time-lapses were taken to quantify nucleation rates of corals in the normal ocean conditions. Reefs play a huge role in supporting biodiversity, economies, and population health. Understanding how nucleation rates are changing in variable ocean conditions is a key step in developing new ways to conserve reefs.

Tabletop Role-Playing Games (TTRPGs) are an increasingly popular group activity known both for their collaborative nature and creative demands. Despite the growing popularity, TTRPGs have yet to escape their reputation as a medium for social outcasts to construct escapist power fantasies. The intent of my research is to show that these “power-fantasies,” can actually become a valuable way to explore political and personal identity. I constructed a TTRPG called Blank Spaces, designed for exploring identity, and played with 6 different groups for 22 hours. After each session, I interviewed the players and used recordings of these sessions to qualitatively analyze player experiences. Players were often surprised that they had unwittingly performed meaningful self-criticism and world-criticism, all while simply enjoying a game. This has demonstrated that TTRPGs can be incredibly powerful self-exploration, critisim, and development tools.

Task prioritization, or choosing which order to do tasks, is an essential skill to possess. However, there are no definitive answers to the question of “how” we prioritize tasks. There are numerous factors that are considered in task prioritization, including a vast array of queuing rules (FIFO or First In First Out, EPT or Earliest Processing Time, etc.) However, many of these systematic methods of prioritization don’t account for task complexity. Another common way to prioritize tasks, which will be the focus of this study, is finding the task that seems the closest in time. This perception of Temporal Distance does address task complexity because we balance task complexity and due date when deciding which task is closer or farther away in time. Though individual Temporal Distance Perception is a widely researched topic, there has not been much research conducted on application in a team setting. Prioritizing one’s tasks individually is difficult, but it gets much harder when others’ schedules need to be factored in as well as an individual’s schedule. In addition to this issue of schedule navigation, this research will take place in a multidisciplinary setting, so teammates will not be able to know in detail how long a teammate’s task will take. This too makes it more difficult to choose which task comes first. My research question is this: How does Temporal Distance Perception in a Multidisciplinary Setting affect Task Prioritization in Teams? I am conducting a synthesis of literatures about Task Prioritization, Multidisciplinary Teamwork, and Temporal Distance Perception, as well as creating a data model based off the synthesis. I was sourced the results of team building exercises from NASA’s Human Research Program, which include a variety of real-world examples of how astronaut teams prioritize tasks.

The link between protein sequence and structure is not always apparent. The dogma is that sequence determines structure, but it is not clear how very different sequences can give rise to the same structure. Here, we employ high temperature molecular dynamics unfolding simulations to probe the pathways and specific interactions that direct the folding and unfolding of the SH3 domain, a family of small proteins consisting of two β-sheets arranged to form a barrel. SH3 domain proteins are involved in various functions including protein binding, cell signaling, and nucleic acid modification. The SH3 metafold consists of 753 proteins with the same structure but varied sequence and function. To investigate the relationship between sequence and structure, we selected 17 SH3 proteins with an average pairwise sequence identity of only 27%. Six unfolding simulations were performed for each protein and unfolding transition states were determined, revealing two unfolding/folding pathways. Transition states were also expressed as mathematical graphs of contacts between chemical groups, and three positions in the transition state structure were consistently more connected to the rest of the graph than other nearby positions. These positions represent a folding hub connecting different portions of the structure in the transition state. Analysis of the multiple sequence alignment and covariation also highlighted positions with high conservation due to packing constraints and long-range contacts. This study demonstrates that the SH3 domain can fold through two distinct pathways, but certain folding/unfolding characteristics are conserved independent of sequence and unfolding pathway. By identifying similar interactions, we demonstrate how different sequences can have the same influence on folding pathway and final structure.

 Hoarseness is a common symptom of multiple laryngeal diseases such as inflammation, paralysis, neurologic disease, or laryngeal cancer. Many patients with these diseases are not diagnosed with the correct underlying cause of the hoarseness early enough. Therefore, healthcare providers need better methods to screen for and evaluate different types of hoarseness. Currently, a combination of tools are used to evaluate voice disorders in specialty clinics such as patient history, perceptual voice evaluation, and laryngoscopy. We want to better understand how providers with different medical backgrounds evaluate patients with voice complaints. We are most interested in seeing how history, perceptual voice evaluation, and laryngoscopy impact decision-making and diagnosis. In addition, our group has developed a machine learning algorithm that analyzes voice to detect the presence or absence of a laryngeal mass. We want to see if this algorithm could be clinically useful for generalist providers. To address these questions, a group of clinician evaluators including general practitioners, otolaryngologists, and speech language pathologists, will be recruited remotely. Subjects will be asked to complete an electronic questionnaire with patient case scenarios, asking them to evaluate hoarse voice samples and laryngoscopy exams, with and without case history. For perceptual voice sample evaluations, clinician performance will be compared to the algorithm’s classification of whether a hoarse voice is from someone with a laryngeal mass. From there we will see if clinician detection of laryngeal masses from voice could be improved with this algorithm. If the algorithm has better performance than clinicians, then it may be clinically useful as a screening tool in the future. Our results will help us understand how evaluations for hoarseness are done and can be improved.

One of the Ultracold Atoms Group’s themes is to study the interaction between trapped ultracold atom mixtures. Certain experiments, such as the study of spin-dependent Feshbach resonance, requires us to select one specific nuclear spin state of the atom from the mixture. This process is achieved by the optical Stern-Gerlach technique, where we use the laser to produce the magnetic field gradient. However, this technique requires us to use the imaging path with relatively poor imaging quality due to, for example, vibrations of the optics. When we normalize these atom images, these vibrations introduce misalignment between images and thus unwanted noises. Hence my project is focused on stabilizing the imaging process by a software implementation of imaging alignment scheme. The code I developed can be seen as the analog to the inner product of two vectors, which characterizes the extent of misalignment between two vectors. This scheme has increased the efficiency of the experimental procedure and at least doubled the signal-to-noise ratio. Its easy implementation provides another route to reduce noises in the data of similar experiments. 

CD8+ T-cell exhaustion during chronic human immunodeficiency virus (HIV) infection is characterized by increasing expression of exhaustion markers on the cell surface that lead to decreased function, greatly diminishing immune responses and therapeutic vaccination efficacy. Blocking the activation of one such marker (PD-1) using a monoclonal antibody (aPD-1) can help reverse exhaustion. We hypothesized that dosing with aPD-1 would boost the immune system and decrease expression of certain exhaustion markers on CD8+ T-cells throughout infection in order to improve therapeutic vaccine responses. To investigate this hypothesis, we studied how exhaustion changed over time in simian-human immunodeficiency virus (SHIV)-infected rhesus macaques treated with a combinatorial therapeutic regimen consisting of a conserved-elements vaccine to circumvent viral mutants, GS986 to reverse latency, CCR5 gene editing to prevent viral entry, aPD-1 to reverse T-cell exhaustion, and antiretroviral treatment. We characterized exhaustion in peripheral blood mononuclear cells (PBMC) with surface staining and flow cytometry, focusing on markers of exhaustion including PD-1, CTLA-4, LAG-3, TIGIT, and TIM-3 at various timepoints throughout SHIV infection and therapeutic vaccination. We observed higher CD8+ T-cell vaccine responses in animals receiving aPD-1, compared to animals that were vaccinated but not given aPD-1, suggesting aPD-1 dosing improved vaccine responses. We did not observe any significant correlation between PD-1 signaling and expression of other exhaustion markers, suggesting that blocking PD-1 does not reduce exhaustion by decreasing the expression of other exhaustion markers. However, we found a significant negative correlation between CD8+ T-cell vaccine responses and the expression of TIGIT (Spearman r= -0.75, p=0.007). As reduced TIGIT on CD8+ T-cells correlated with increased vaccine responses, there may be a role for dual TIGIT and PD-1 blockade in future studies. Defining the role of CD8+ T-cell exhaustion in therapeutic vaccine immunogenicity and efficacy is crucial to improving combinatorial immunotherapy towards a cure for HIV.

Currently, there is no clinical best practice in place to support and manage follow up care for previvors, individuals who have tested positive for one or more mutations that increase cancer risk. Patients and providers need support in making complex decisions about follow-up. This project aims to design ‘previvor plans’, modeled after survivorship care plans received by cancer survivors, to help inform and support previvors after they receive a positive test result. Content of the previvor plans includes recommendations for screening, prophylactic surgery, pharmacological interventions, and lifestyle changes based on national guidelines as well as resources to receive further education and support. This project is a part of a larger study which evaluates two different methods of engaging patients in genetic testing for cancer risk across 12 different primary care clinics. Each patient in the study who tests positive for a mutation that increases cancer risk receives a previvor plan tailored with resources and recommendations specific to their test results and location. Use of the plans will be evaluated through surveys and interviews of previvor patients. If successful, the creation of previvor plans will provide a tool which can be used by patients and their providers to manage follow up care after receiving a positive test result.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by the presence of repetitive patterns of behaviors and deficits in social communication and interaction. Attention to social information is a key component of the development of social communication. Previous studies used eye tracking to examine visual scanning patterns associated with social attention in children with ASD and neurotypical children. Eye tracking is used to both identify the atypical patterns of social attention and to predict clinical outcomes in ASD. Although atypical eye gazing patterns are considered as potential biomarkers, researchers commonly consider data loss in eye tracking as error or noise, and rarely investigate it more thoroughly. In this proposal, we hypothesize that loss of data is a potential signature of core social motivation issue when a social video is playing, and, rather than being a nuisance variable, which reflects the broader continuum of social attentional-motivational challenges faced by individuals with ASD. We used eye tracking to confirm previous findings on atypical attention patterns, and further utilize behavior coding to examine the three types of causes of data loss including blinking, non-compliant behaviors, and technical error. We hypothesize that data loss due to blinking is associated with a lack of social motivation and that data loss due to non-compliant behaviors is associated with executive function. Social motivation and executive function were measured by parent reports. Exploring data loss in eye tracking may help reveal comprehensive and fundamental factors of diminished social motivation and neurocognition in ASD.

Hoarseness is a common symptom reported to generalist healthcare providers, with approximately 1% of the clinical population being affected by it each year. It can be caused by multiple etiologies, such as hoarseness due to a cold, acid reflux, or laryngeal cancer. Perceptual evaluation of the voice is inaccurate, and it is therefore difficult to differentiate between hoarseness requiring urgent referral for specialty evaluation (i.e. laryngeal cancer) versus a disorder that could be managed without specialty care (i.e. acute laryngitis). The current gold standard of diagnosis for hoarseness is laryngoscopy, an in-clinic endoscopy recording of the larynx performed by an otolaryngologist specialist. Our research team seeks to improve perceptual voice evaluation by developing and testing machine learning algorithms which analyze voice for underlying pathology, beginning with an algorithm which screens voice for laryngeal masses. We hypothesize that our algorithm will have greater than 80% sensitivity and specificity in the classification of voice samples from patients with laryngeal masses. To test this, we are developing a large, prospective database of voice samples from a laryngology clinic using a smartphone application. Subjects are adult patients presenting to the laryngology clinic, with and without voice disorders, who have had a recent laryngoscopy exam and no laryngeal surgery within the past three months. We are collecting patient history which could influence voice quality, such as age, gender, alcohol use, smoking history, and subject-perceived voice disorder impact. After collection of the voice sample and patient history, cases are classified into underlying pathologic categories. We see recruitment of a well-classified and prospective patient population with a range of voice disorders. This work could lead to improved screening of patients with hoarseness in underserved and primary care settings, and more appropriate and timelier specialist referrals and treatment.

The maternal bond is an intimate attachment between a primary caregiver (PC) and their infant which provides the infant with security, facilitating physical, social, and emotional development. A sensitive and responsive environment, such as the presence of healthy maternal bonds, guides an infant’s neurodevelopment. Changes in mood and emotional state can alter the care a PC provides and cause difficulties in bonding with their infant, impacting the baby’s psychological and physical development. In infants, the mechanisms by which development may be impacted are unknown. Recently, research has shown early atypical attention to visual pop-out in autism spectrum disorders. Attention to visual pop-out describes our cognitive ability to quickly identify differing objects presented among similar looking ones. In this project, we investigated whether PC mental health affects attention to visual pop-out in infants. Participants included 50 infants who were assessed at 6 and 12 months of age. PCs completed the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) at both timepoints. Infants watched a 4-minute visual pop-out paradigm, which included social (face) and non-social (shape) trials. We assessed responses to visual pop-outs and explored whether BDI and BAI scores correlated with visual pop-out performance at 6 and 12 months. We also investigated whether BDI and BAI scores influenced the development of attention to visual pop-out between 6 and 12 months. We hypothesized infants of primary caregivers who report more (a) depressive and (b) anxious symptoms will demonstrate weaker identification of the pop-out during social trials compared to their peers but be unaffected during nonsocial trials. This study will help deepen our understanding of the impact of maternal depression and anxiety on infant development and help health providers identify and support families.

Recent work published by my colleagues and I showed that diagnostic ultrasound, applied directly over the visual cortex of human participants, increased the likelihood that they would observe visual effects while looking at a visual target, with that likelihood increasing over the course of the experiment. However due to a lack of EEG data, it is impossible to know the biophysical mechanisms and neural pathways that generate the observed effects on brain function. To better understand the full effect and mechanism of our initial findings, I helped develop a surgical protocol for a mouse model allowing for the collection of EEG data while exposing the animal to a combination of light and diagnostic ultrasound stimuli. EEG data was collected from 5 mice using a stimulus paradigm that we believed would increase the rodent's susceptibility to light stimulus. I utilized Matlab for processing, visualization, and statistical analysis of the data to determine the effects and hypothesize potential biophysical mechanisms of the stimuli. My analysis focused on determining whether the ultrasound stimulus successfully increased the susceptibility of the visual cortex, and which brain frequency bands were modulated by the stimulation.

The MAJORANA experiment and its follow-on, the Large Enriched Germanium Experiment for Neutrinoless Double-Beta Decay (LEGEND), search for the creation of matter in the form of neutrinoless double-beta decay, a process that would demonstrate that neutrinos are their own antiparticle and that lepton number conservation may be violated, allowing a deeper understanding of the matter-antimatter imbalance in the universe. MJ60 is a germanium detector used to investigate the low-energy region of the MAJORANA DEMONSTRATOR data, as well as the waveforms produced from incident betas in comparison with gamma events. The latter of these is important for understanding the background of LEGEND: the detectors are submerged in liquid argon, in which beta decays of argon-39 and argon-42 contribute to the background of the extremely sensitive experiment. MJ60 was originally a prototype for the P-type point-contact detectors used in the MAJORANA DEMONSTRATOR. Our group is using this detector to measure mechanisms of energy loss near the detector surfaces by recording events from the nearly monoenergetic beta emissions of metastable krypton-83 (83Kr) at 18 and ~30 keV. Analysis of the waveforms produced from these events, which has been my primary task, will allow us to investigate whether betas incident on our detectors’ passivated surface exhibit markedly different charge collection than gammas, as has been hypothesized. If this expectation is upheld, we will be able to produce a method to identify these events based upon a calculated parameter from the recorded waveforms. Such a parameter will help inform future detector R&D efforts, and will also contribute to background rejection capabilities in MAJORANA and LEGEND.

The COHERENT experiment is endeavoring to detect Coherent Elastic Neutrino-Nucleus Scattering (CEνNS) in several nuclear targets using the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory (ORNL). We search for very low energy (on the order of keV) coherent interactions between neutrinos and atomic nuclei using an array of particle detectors made of different scintillating materials. Neutrinos are fundamental particles under the Standard Model of particle physics that historically have not conformed to theoretical expectations. Understanding their interactions with other particles helps us potentially find other unexpected qualities of neutrinos and in that, discover new physics. At the UW component of the COHERENT team, I along with several other physics undergrads, have just finished characterizing over one-hundred NaI(Tl) crystals to contribute to a large array of detectors at ORNL where they will be illuminated by a strong, pulsed flux of neutrinos born from pions and muons generated in the SNS beam target. For each crystal, I used two characteristic radioactive sources (133Ba & 137Cs) to gather data on each crystal for characterization of their use at ORNL. Each crystal was run for 1.67 hours to find the optimal operating voltage (gain) and to explore the energy linearity of radiation detections at different points in each 7kg crystal (this allowed us to identify if the crystals had any cracks that would interfere with detections). In this talk, I intend to present the statistics on the measured crystal characteristics, including gains, energy resolution, scintillation uniformity as we prepare to ship the crystals to ORNL for installation in the array of other detectors capable of detecting the CEνNS phenomenon.

Since the Industrial Revolution, human-caused (anthropogenic) emissions of greenhouse gases and pollutants, including sulfur, have changed the composition of the Arctic atmosphere. Greenhouse gas emissions and climate feedbacks have resulted in an Arctic amplification, the phenomenon of rapidly warming Arctic temperatures and of sea-ice extent declining at a rate of 7.2% per decade since the 1980s. Other anthropogenic emissions, such as sulfur aerosols, can reflect sunlight and increase cloud cover, temporarily decreasing temperatures. Since the 1980s, clean air policies have reduced the emissions of sulfur aerosols, which have contributed to Arctic amplification. The majority of Arctic sulfate aerosols come from anthropogenic emissions, but natural sources include sea salt, volcanoes, or biological activity. Sea-ice algae produce dimethylsulfide (DMS), which converts to sulfate aerosols through oxidation in the atmosphere. With the decline in sea-ice extent, the habitats of Arctic biota such as algae are diminishing, and it is unclear how declining sea ice will affect biogenic sulfate aerosols and DMS emissions in the future. Here we investigate the relationship between sea-ice extent decline and DMS emissions thorough analysis of an ice core collected in Summit, Greenland to understand the relative contribution of biological activity to Arctic aerosol abundance. To analyze the biogenic sulfate in the ice core, we concentrate ice core meltwater samples, precipitate sulfate in the concentrated sample solution, measure the sulfur isotopes on a stable isotope mass spectrometer, and run GEOS-Chem model simulations to interpret the observed trends. The isotopes of sulfur in sulfate indicate what portion of the atmospheric sulfate aerosols result from biological activity. We hypothesize that biogenic sulfate has decreased with declining sea-ice extent due to the reduction of sea-ice habitats for sea-ice algae. The response of Arctic sulfate aerosol abundance to the decline of sea ice holds implications for the future of Arctic amplification.

Members of the genus Psychrobacter, within the class Gamma-proteobacteria, generally live in very cold marine habitats. These bacteria can be found in Arctic and Antarctic sea ice and sediments, in deep-sea environments, and in permafrost containing relic marine sediments (cryopeg). Each of these environments provides a different combination of temperature and salinity, with different strains of Psychrobacter spp. potentially adapted to grow at different rates depending on environmental source and in situ conditions. I am exploring the growth characteristics of two Psychrobacter spp., each isolated from a different extreme environment. Psychrobacter sp. nov. strain CB7C was isolated from cryopeg brine (originally at –6°C and 140 ppt), and Psychrobacter sp. nov. strain 7E was isolated from winter sea ice brine (originally at –12°C and 128 ppt). We incubated strain CB7C in duplicate at 57 different sets of temperature and salinity conditions, including 19 temperatures, ranging from –7 to 12°C, and salinities of 35, 75, and 120 ppt. The strain was grown in a complex medium, Marine Broth 2216 (at 50% organic strength), adjusted to desired salinity. At regular intervals during the incubations optical density was measured, with cell counts made at start and end. Calculated growth rates and cell yields for CB7C varied across the different temperatures for each salinity. At higher salinity, the temperature at which the bacteria showed maximal growth shifted downwards, a result consistent with in situ conditions (lower temperatures at higher salinities) but novel in microbiology. By conducting similar incubations with strain 7E I will be able to compare growth patterns of the two isolates across a wide set of temperatures and salinities and determine if results with CB7C are singular or represent a more common trait amongst Psychrobacter strains, helping to explain their prevalence under such extreme conditions.

Back contact solar cells improve on the standard geometry by arranging both the positive and negative electrodes on the back of the device. This significantly improves efficiency by eliminating three critical challenges faced by typical solar cells: (1) shading of the active layer by top contacts, (2) the conflicting requirement for conductive yet transparent top contact materials, and (3) difficulty in printing metallic contacts onto the sensitive photoactive layer. Electrodeposition is a disruptive method that offers an alternative pathway for solution processing manufacturing, but is relatively unexplored as a method of fabricating perovskite back contact solar cells. This study focuses on achieving selective electrodeposition of high quality nanoscale electron and hole transport layers (tin and nickel oxides respectively) onto interdigitated silver collectors. In this investigation, a silver working electrode and a nickel or tin counter electrode against a silver/silver chloride reference electrode comprise a three-probe system in nickel nitrate and tin chloride electrolyte baths. The conductivity and carrier mobility of the electrodeposited transport layers are discussed as a function of salt and dopant molecule concentrations in the electrolyte bath. High carrier mobility layers are desirable for increased solar cell efficiency. The microstructure and thickness of the transport layer are discussed as a function of bath temperature, stirring speed, and the magnitude and duration of the supplied current density. The transport layers are characterized using optical profilometry and scanning electron microscopy. Diode devices are fabricated to characterize the electrical properties of the oxide layers. Based on these results, an optimal electrodeposition procedure is recommended for producing high quality nickel- and tin-based charge transport layers for application in back contact perovskite solar cells. Achieving this device geometry via electrodeposition enables the production of more efficient solar modules using high throughput manufacturing methods - bringing novel photovoltaic materials one step closer to widespread use.

Humanity is on the verge of a biotechnological epoch. What this will entail is a union of opposites: biological humans merging with artificial machines. Unity of opposites, or non-duality, is a timeless theme, one that is not only found in the ancient teachings of Heraclitus or in Greek mythology, but also in that of the I-Ching, and the Tao Te Ching. The yin-yang symbol is one of the earliest visual depictions of this. Support for a unified theory of the universe is now being widely embraced; hence the shift from the old Standard Model of particle physics to the new Core Theory. Modern interpretation of what Laozi referred to as, Tao, suggests a process that is characteristic of a double torus, with a cuboctahedron at its heart. Such a synergic principle would not only be observable in the nature of matter, but also in that of the mind. It is of no coincidence that humanity is beginning to integrate with arguably its finest of achievements—tools. Synergic inquiry is the method by which this literature review will be conducted, so as to build the argument that all things are interdependently connected, distinguishable sub-systems of a larger system. This implies that the convergence of human and machine is simply the beginning of a brand new, distinguishable part in that whole. The study of synergetics, in its wider applications, proves to be an invaluable tool to understand the macrocosm and microcosm relationship, and it will no doubt contribute greatly to the symbiotic relationship between nanotechnology and molecular biology, as humanity seeks to build a better world.

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen associated with worsening disease outcomes in cystic fibrosis (CF) patients. P. aeruginosa uses quorum sensing (QS), a cell-cell signaling system, to control expression of a variety of genes including virulence factors. In P. aeruginosa, QS is mediated in part by acyl-homoserine lactone (AHL) signals that can diffuse in and out of cells. Once AHLs accumulate, they bind to a receptor regulator that activates gene transcription. P. aeruginosa has two complete AHL QS systems, LasI-LasR and RhlI-RhlR. The two systems are arranged in a hierarchy, with the las system controlling the rhl system. QS activation in P. aeruginosa is restrained by cellular proteins that dampen the QS response. These proteins, known as “anti-activators”, attenuate QS by preventing receptor activation. Three anti-activator proteins, QscR, QslA, and QteE, have been identified in P. aeruginosa. These anti-activator proteins have additive, overlapping roles in repressing expression of QS gene products in laboratory strains but their role in the QS dynamics of CF isolates is still unclear. This project used standard molecular cloning techniques to delete or overexpress anti-activator genes in a selection of clinical isolates from CF patients. A reporter plasmid with a fluorescent marker was used to track the activity of LasR and RhlR. These experiments were used to quantify differences in QS-controlled gene activation. To test the hypothesis that anti-activators decrease the amount of LasR in the cell, Western blots were used to assess the cellular levels of QS receptors. In strains with deleted anti-activator genes, LasR levels were higher and induction was earlier. Additional tests for phenotypes controlled by QS, such as protease and pyocyanin production, were also performed. Future research should focus on evaluating these effects in additional CF isolates.

Throughout history, human-induced habitat loss, pollution, and hunting have pressured mammals to adapt to lifestyles that limit human interaction. When humans threaten wildlife, a fitness advantage is provided to animals who avoid human interaction. But what about in protected regions where these threats are limited? Cocha Cashu Biological Station, located in Manu National Park, is an example of one of these regions. While native communities continue to hunt within the research station, overall levels of hunting, deforestation, and pollution, are significantly lower than in the surrounding unprotected areas. Our research team chose to design a study in Cocha Cashu to analyze terrestrial mammal distribution in relation to human habitation in areas where human threats have historically been limited. Our hypothesis was that mammal abundance would increase with distance from human habitation. Our study design involved a northern and eastern transect with a near (N), medium-distanced (M), and far (F) trap location. Each trap location had both a sand and camera trap, and data was collected from the traps morning and night for four consecutive days. On the eastern transect, there was a positive linear relationship between distance from human habitation and number of mammals observed (N: 2 mammals, M: 4 mammals, F: 8 mammals). On the northern route, the highest number of mammals was observed at the medium-distanced location (N: 1 mammal, M: 7 mammals, F: 3 mammals). Overall, our data did not support our hypothesis that mammal abundance increases with distance from human habitation in protected areas. Our results do, however, provide a platform for further research on resource accessibility and its potentially larger influence on mammal distribution patterns than the influence of human habitation.

Antiretroviral therapy (ART) cannot eliminate latently infected human immunodeficiency virus (HIV) reservoirs, the barrier to HIV cure. A “shock and kill” strategy has been proposed to cure HIV by using latency-reversing agents (LRAs) to reactive latent proviruses and allow for reservoir elimination. Due to the low potency and high toxicity of LRAs, none have yet been effective in reducing reservoir size in vivo. Here, we hypothesize that delivery of LRAs using nanocarriers (NCs) will improve drug solubility and safety, provide sustained drug release, and simultaneously deliver multiple drugs to reservoir tissues and cells. We developed hybrid nanocarriers to incorporate physicochemically diverse LRAs and target reservoirs in lymphatic CD4+ T cells. LRAs were formulated by physical encapsulation or covalent conjugation to the biodegradable polymer (PLGA) core. Drug combinations were evaluated in vitro using a J-Lat reporter cells and validated in CD4+ T cells from virologically suppressed patients. CD4+ T cell targeting specificity was tested ex vivo in non-human primate (NHP) peripheral blood mononuclear cells (PBMCs). Targeting and toxicity were also evaluated in vivo in mice following size optimization for increased passive drainage to lymph nodes. Optimized nanocarriers were used for identification of an LRA combination displaying synergistic latency reversal and low toxicity in vitro in model and patient cells. Long-term and specific activation of CD4+ T cells in NHP PMBCs ex vivo and in mouse lymph nodes in vivo was observed, with significant reduction in toxicity compared to free LRA delivery. This nanocarrier platform targets CD4+ T cells, successfully inducing latency reactivation in HIV reservoirs. The platform additionally enables new solutions for HIV cure with the potential to deliver anti-HIV agents, vaccines, immunomodulating agents, and gene-modifying oligonucleotide drugs.

In trying to understand biology’s dynamic heterogeneity, scientists have sought to recapitulate the spatial complexity and temporal presentation in which proteins are naturally presented to cells. Currently, the most promising strategies in this regard exploit sequential ligation/cleavage reactions, each controlled in time and space using light so as to reversibly immobilize proteins within synthetic biomaterials. Though our lab has utilized these approaches to spatially control complex biological fates with micron-scale resolutions, previous methods suffer from complex syntheses, as well as requirements for specialized equipment and skillsets rarely available in bio-based laboratories. Improving upon these fundamental limitations, our group has developed a scalable system wherein proteins can be bound/released from hydrogels using light, without the need for such expertise/equipment, by being fully genetically encodable. In this approach, biology performs all the modifications necessary to photopattern protein binding to gels, as well as install the reactive species requisite for the protein’s photo-mediated release. We have accomplished this using a photoactivatable protein-peptide ligation reaction developed by our lab, wherein UV irradiation “activates” the protein to ligate specifically with the peptide tag. Additionally, we exploit co-translational chemoenzymatic modification strategies to install a functional handle for tethering the protein into polymeric hydrogels during protein expression. To the peptide tag, we append a photocleavable protein that cleaves when irradiated by visible light, fused to a protein of interest (POI) to be tethered to the hydrogel. Expressing these proteins in E. coli yields the first-ever fully genetically encodable system which can reversibly pattern proteins into hydrogels, by first shining UV light to tether POIs into biomaterials, then subsequently shining visible light to photocleave the protein and trigger POI release. Highlighting the system’s versatility, we demonstrate that the approach is compatible with fluorescent proteins and bioactive growth factors to direct 4D cell fate.

Water-swollen polymeric networks (i.e., hydrogels) provide a structural platform for the manipulation of chemical and mechanical signals that mimics the complex heterogeneous environment experienced by cells in vivo. Photoresponsive chemistries have been of particular interest to this end, as they allow for precise spatiotemporal control of physiochemical properties and, thus, cell behavior. Here, we present a novel protein-based network that will allow for the photo-mediated stiffening of genetically-encoded hydrogels. In this system, we exploit a biochemical technology recently pioneered by our lab in which two pairs of proteins undergo irreversible, covalent heterodimerization after photoactivation. Through the incorporation of an inert, unstructured polypeptide backbone, we have exploited the aforementioned reaction to induce gelation in response to light through the formation of four-arm protein crosslinks. Unlike previous synthetic polymer-based hydrogel systems, this system is entirely genetically encoded, which provides significant advantages in terms of cost, time, and production simplicity. As we intend to demonstrate through photorheometry, this reaction proceeds in a dose-dependent manner, providing step-wise control of both where and when gel stiffening occurs. Such 4D control of a gel’s mechanical properties can be used to influence cell migration, growth, and differentiation, and, thus, could have applications in tissue engineering. Furthermore, we anticipate our system could be utilized to model the stiffening of the extracellular matrix, which is commonly associated with pathologies such as cancer, fibrosis, and cardiovascular disease.

Many universities do not have separate language courses for heritage language (HL) learners and second language (L2) learners, and over the last decade, an increasing amount of HL students have been enrolling in the same language classes as their L2 peers. How does the same heritage language learner engage in Spanish classroom pair work activities when working with a heritage versus a second language learner? Student engagement drives learning. If one population shows low engagement, it is detrimental to their learning. In this project, we are analyzing engagement as a multidimensional construct which includes the branches of cognitive, behavioral, emotional, and social engagement. The participants in our case studies are HL and L2 learners taking equivalent upper level university Spanish courses, the former in a course designed for HL students, and the latter in one for L2 students. I hypothesize that a heritage language learner will be most engaged when working with another heritage language learner. Their skill levels will be the most similar, so they will have a level of ease and comfort with each other, and will relate to each other more. I am tracking behavioral engagement by number of words, number of turns, overlapping speech, and latched speech, in which there is no pause between the speakers’ turns. Emotional engagement appears as turns including laughter. Lastly, I am marking social engagement through content-related and language-related questions, co-construction of ideas, and repetition of ideas, which may include an error correction. My research will contribute to understanding of interactions between matched and mixed dyads, which is important information for language teachers and the teaching practice.

Cancers are broadly characterized by changes in cell metabolism. Tumor cells typically exhibit functional respiration and inhibition of electron transport chain can impair cancer cell proliferation. However, certain neuroendocrine cancers can arise from loss of function (LOF) mutations in succinate dehydrogenase (SDHx/complex II), which plays a key role in the TCA cycle and in mitochondrial respiration. SDH, which catalyzes the conversion of succinate to fumarate, comprises four subunits: A, B, C and D. LOF mutations in subunits B, C, and D can promote tumorigenesis and mutations in subunit B (SDHB) are particularly associated with malignant and metastatic neoplasms. Interestingly, SDHB impaired cells show an accompanied loss of activity in complex I, implying that unlike the majority of cancer cells, respiration is not essential and may even be antagonistic for SDHB mutant cancer cell proliferation. Indeed, preliminary experiments indicate that inhibition of complex I can restore proliferation to cells treated with an SDH/complex II inhibitor. However, the molecular mechanisms behind this phenomenon are not well understood. We aim to investigate the metabolic mechanisms by which dysfunctional respiration is essential for the proliferation of SDH impaired cells. We hypothesize that inhibition of respiration in these cells can prevent oxidation of NADH to NAD+ at complex I and alter the redox homeostasis in the mitochondria to support proliferation. Specifically, we will test to see if increasing the NADH/NAD+ ratio is the required function of complex I inhibition that rescues cell proliferation in SDH impaired cells. In addition, we will characterize the metabolic consequences of specific alterations SDH, complex I, and mitochondrial redox state. Results from this study should allow us to delineate the importance of metabolic alterations in SDH mutant cancer cells and potentially help identify metabolic vulnerabilities for treatment of SDH impaired cancers.

Human papillomaviruses (HPV) contribute to approximately 4.5% of cancer cases worldwide. There are currently three vaccines which protect by producing neutralizing antibodies to the structural capsid protein, L1, for each of the most oncogenic HPV types. Despite the high protective efficacy of these vaccines, not enough is known about the antibodies elicited. The aim of this project is to clone and characterize HPV-specific human monoclonal antibodies after vaccination, particularly antibodies reactive to types other than 16 and 18. Plasma cells and memory B cells were isolated from vaccinees at different time points following HPV vaccination. Antibody-encoding transcripts were amplified from pre-screened plasma cells and cloned into expression vectors - one for each antibody light and heavy chain. The expression vectors were co-transfected and the proteins were harvested and purified for one of the antibodies of interest. Antibodies reactive to HPV types 6, 11, 16, 18, 31,33 and 58 were identified. The first antibodies in the process of cloning were reactive to HPV type 11.The findings of this study will allow us to use these monoclonal antibodies as reference standards to determine the quantity of antibodies in serological assays, thus helping us identify the binding affinity and neutralizing capacity of vaccinees’ antibodies. This will aid future studies aimed at answering the question of whether the vaccine doses can be reduced to one, instead of two or three doses.

The existence of 'checkpoints' in the mitotic cell cycle is well characterized; however, much less is known about the possible existence of checkpoints controlling re-entry of terminally differentiated cells into mitosis. We are exploring this possibility in Chlamydomonas reinhardtii, a unicellular eukaryotic green alga that, in the presence of visible light, differentiates back and forth from an actively dividing 'vegetative' state to a non-dividing 'gametic' state depending on the presence or absence of nitrogen in the culture medium. The work of previous students in our group suggests that gametes of wildtype C. reinhardtii show a growth delay of about 12 hours after nitrogen is added to nitrogen-deficient media; UV exposure immediately prior to nitrogen addition significantly increases the length of this delay. This is consistent with the working hypothesis of a dedifferentiation checkpoint in this organism. However, the visible light requirement for dedifferentiation confounds this result, because C. reinhardtii also uses visible light for photoreactivation subsequent to UV exposure. To control for this, we are taking a genetic approach. We expect to find an even longer post-UV dedifferentiation lag for a photorepair-deficient mutant of C. reinhardtii compared to wildtype, which would strengthen the case for a dedifferentiation checkpoint in this organism. Of particular interest in the present study is our use of two parallel statistical approaches to analyze our experimental data: (1) a 'traditional' timepoint-by-timepoint statistical analysis, and (2) statistical comparison of logistic curves fitted to the same data. We have written programs that facilitate execution and comparison of the outcomes of both methods of analysis, and expect both methods to agree in confirming our hypothesis. This insight into the inner workings of cell cycle dedifferentiation, as well as the validation of the second, novel statistical approach could be beneficial to a broad variety of ecological and biomedical experimental contexts.

Training a nonhuman primate (NHP) for research experiments generally requires the NHP to spend large quantities of time learning experimental tasks outside their home environment, and this requires a human researcher to be present at all times during training sessions. The purpose of this project is to create a wireless, semi-autonomous, low cost, cage-side training reward system allowing NHPs to train on experimental tasks for extended periods of time without the presence of a human researcher. An ideal device would allow for wireless data collection and provide both real-time and post-training information on the NHP’s training progress. Exposing NHPs to tasks first in the low-stress environment of their home cage before exposing them to the same task in an experimental booth can potentially speed up training processes. This lets research laboratories maximize researcher time and efficiently use equipment. Our cage-side training reward system consists of an iPad displaying touchscreen tasks, a speaker supplying audial cues for the tasks, an automatic feeder administering treats to the NHP for correct performance, and a computer to control the touchscreen tasks and collect data with custom MATLAB code. The iPad and computer communicate via a Wi-Fi router and this router also communicates with a Wi-Fi receiver which runs the feeder and speaker. The connection methods give the ability for wireless communication through walls, allowing the researcher to run tasks semi-autonomously from a computer outside the animal room. Excluding the costs of the iPad, computer, and MATLAB license, the system is estimated to cost under $300. Two rhesus macaques have undergone cage-side training with this device and have subsequently transitioned smoothly to learning tasks in a traditional experimental booth. In conclusion, this device serves as a low-cost method to enhance the training process for non-human primates while saving time and resources of the research laboratory.
 

 Loss of tooth mineral, demineralization, is the root cause of dental ailments - the most prevalent health problems affecting over 90 percent of Americans. These range from white spot lesions, the earliest sign of dental demineralization, to periodontal diseases, which can lead to more serious health issues. Current restorative treatments of tooth structure and function utilize synthetic materials, e.g. amalgam, glass ionomers, and particle reinforced resin composites that lead to deposited secondary precipitates. Although these common procedures are well-established and relatively effective, their durability is limited due to lack of structural and functional integration of deposited layer with the underlying tooth. GEMSEC labs have developed a proprietary technology dubbed “peptide-guided remineralization” which enables the formation of a new mineral with protein-derived peptides. Using this technology, the lab teams have successfully restored dental hard tissues via several case studies including enamel, cementum, dentin under in vitro and in vivo conditions. Translating this technology into a daily-use product, we developed a prototype, dental lozenges, designed to aid in enamel remineralization using a biomineralizing peptide, ADP5, derived from amelogenin, the key enamel protein. Herein we aim to refine the lozenge formulation through an iterative study for enhanced durable and whitening remineralized layer. Remineralization performance of different tablet formulations were tested in artificial saliva using extracted human enamel teeth. The samples were characterized using SEM showing that the current lozenge formulation creates a new mineral layer on enamel up to 2 µm in thickness. In summary, the new lozenge artificially regenerates lost enamel on the molecular level to treat tooth decay and erosion. Developed through a simple biomimetic methodology, this prototype lozenge could be mass fabricated for the consumer dental care market and expanded to include dental varnishes, gels, and pastes.

 The number of older adults ≥65 years with bothersome pain has increased in the past decade due to an increase in population size and life expectancy of older adults. Amongst several factors studied that may contribute to pain prevalence, socioeconomic status(SES) has been concluded in most studies to be more directly associated with pain prevalence rather than race/ethnicity. The objective of this project was to determine how physical function, due to pain, varies by race/ethnicity. We conducted a retrospective secondary analysis on the National Health & Trends Study(NHATS) to determine how Short Physical Performance Battery (SPPB) scores and secondary pain outcomes differed by race/ethnicity amongst participants who reported bothersome pain in 2011. Baseline race/ethnicity characteristics were gathered to characterize cohort. SPPB score and secondary outcomes for white(NH), black(NH), and hispanics were described for Rounds 1&2. Weighted, regression analysis were performed on SPPB scores to adjust for covariates using survey features. Results show a meaningful difference of SPPB scores among racial/ethnic groups that prompts for more research as to what factors may play a role in differences on the impact of pain on physical function by race/ethnicity.